View/Open

Issue Date

2010-02

Author

Ortiz, Andrea Naomi

Kurth, Benjamin J.

Osterhaus, Gregory L.

Johnson, Michael A.

Publisher

Wiley

Type

Article

Article Version

Scholarly/refereed, author accepted manuscript

Rights

This is the peer reviewed version of the following article: Ortiz, A. N., Kurth, B. J., Osterhaus, G. L. and Johnson, M. A. (2010), Dysregulation of intracellular dopamine stores revealed in the R6/2 mouse striatum. Journal of Neurochemistry, 112: 755–761. doi:10.1111/j.1471-4159.2009.06501.x, which has been published in final form at http://doi.org/10.1111/j.1471-4159.2009.06501.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

Metadata

Abstract

Huntington’s disease is a fatal, neurodegenerative movement disorder characterized by preferential and extensive striatal degeneration. Here, we used fast-scan cyclic voltammetry to study the mobilization and efflux of reserve pool dopamine in striatal brain slices from Huntington’s disease model R6/2 mice. When applying stimulus trains of 120 pulses, evoked dopamine release in wild-type slices was greater than that in R6/2 slices at the higher frequencies (50 and 60 Hz). To quantify cytosolic and reserve pool dopamine levels, amphetamine-induced dopamine efflux was measured after pre-treatment with either tetrabenazine or alpha-methyl-ptyrosine. Slices from 12-week old R6/2 mice released less dopamine than slices from wild-type
mice, while no difference was noted in slices from 6-week old mice. The vesicular release of reserve pool dopamine, mobilized by treatment with cocaine, was shorter lived in R6/2 slices compared to wild-type slices even though peak dopamine release was the same. Moreover, the number of dopamine reserve pool vesicles in R6/2 mice was less than half of that in wild-type.
Therefore, our data suggest that the same number of dopamine molecules are present in each reserve pool vesicle in WT and R6/2 mice and that these vesicles are readily mobilized in both genotypes; however, R6/2 mice have fewer dopamine reserve pool vesicles available for mobilization.